“Signal-on” electrochemical detection of BACE1 for early detection of Alzheimer’s disease

β-Secretase, the β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1), is a key hydrolytic enzyme in the pathway of β-amyloid (Aβ) production in the brain of a patient with Alzheimer's disease (AD). BACE1 is considered a promising biomarker for the early detection of AD. A ferrocene probe (Fc-Probe) is synthesized, where the aldehyde group on the probe can specifically recognize the N terminus of the APP peptide fragment. The sensor's design involves gold nanoparticles (AuNPs) on a glassy carbon electrode (GCE) surface, which allows for the binding of the APP peptide fragment. When BACE1 cleaves the acetylated APP peptide, the N terminus is exposed and triggers an electrochemical signal from the Fc-Probe. The developed sensor can detect BACE1 in a range of 0.02 to 50 U/mL, with a detection limit of 8.0 mU/mL. Such a BACE1 sensor provides a simple, sensitive, and low-cost detection methodology, enabling the "signal-on" detection of BACE1 activity.